The majority of breast cancers occur in postmenopausal women, with 75% of these tumors being estrogen dependent as defined as estrogen receptor (ER) positive. Tamoxifen, an anti-estrogen, has been the mainstay of treatment for hormone-dependent breast cancers. However, recent clinical trials have shown that inhibitors of aromatase, which catalyze the rate-limiting step of estrogen biosynthesis, may be more effective than tamoxifen in treating hormone-dependent breast cancers in postmenopausal women. Unfortunately, resistance to both these endocrine therapies is inevitable in metastatic breast cancer.
We have screened derivatives of plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone) against various human cancer cell lines and we have determined that a derivative acetyl plumbagin (“AP”) is active in breast cancer cell lines models. Further, we have shown that AP has several advantages over Tamoxifen in these cell line models. See U.S. Patent Application Document No. 20140107196, which is incorporated herein in its entirety.
There remains a compelling need to develop more effective therapies for breast cancer patients, particularly those with acquired anti-estrogen resistance, in addition to those with intrinsic resistance to anti-estrogen and anti-HER2 therapies.